What are the considerations for using Empagliflozin (Empagliflozin) in non-diabetic patients over 55 years old with established cardiovascular disease?

Empagliflozin in Non-Diabetics Over 55 Years Old with Established Cardiovascular Disease

Empagliflozin is strongly recommended for non-diabetic patients over 55 years old with established cardiovascular disease due to its significant benefits in reducing cardiovascular mortality, heart failure hospitalizations, and improving quality of life, regardless of diabetes status. 1, 2

Cardiovascular Benefits in Non-Diabetic Patients

Empagliflozin provides substantial cardiovascular protection in patients with established cardiovascular disease, with benefits extending beyond glycemic control:

• Reduction in cardiovascular mortality: The DAPA-HF trial showed that SGLT2 inhibitors reduced cardiovascular death by 18% in patients with heart failure, with consistent benefits regardless of diabetes status 1
• Reduction in heart failure hospitalizations: SGLT2 inhibitors demonstrated a 35% reduction in heart failure hospitalizations in patients with established cardiovascular disease 1
• Improvement in quality of life: Significant improvements in symptoms and physical limitations in patients with heart failure 1

These benefits appear to be a class effect of SGLT2 inhibitors and are independent of glucose-lowering effects, making them appropriate for non-diabetic patients 1.

Evidence Supporting Use in Non-Diabetics

The DAPA-HF trial provided compelling evidence for SGLT2 inhibitor use in non-diabetic patients:

• 45% of participants did not have diabetes
• Benefits were consistent regardless of diabetes status
• Primary composite outcome of worsening heart failure or cardiovascular death was reduced by 26% (HR 0.74 [95% CI 0.65–0.85]) 1

Similarly, the EMPEROR-Reduced trial showed:

• Approximately 50% of subjects did not have diabetes
• 21% reduction in the primary outcome of cardiovascular death or heart failure hospitalization
• Consistent effects in people with or without diabetes 1

Patient Selection Criteria

For non-diabetic patients over 55 years old, empagliflozin should be considered when they have:

• Established atherosclerotic cardiovascular disease
• Heart failure (with either preserved or reduced ejection fraction)
• Chronic kidney disease with albuminuria
• Multiple cardiovascular risk factors 2

Dosing and Administration

• Starting dose: 10 mg once daily
• Can be increased to 25 mg daily if needed and tolerated
• No dose adjustment required based on age alone
• Renal function considerations: preferred eGFR ≥30 mL/min/1.73m² 2, 3

Monitoring and Safety Considerations

Despite the absence of diabetes, non-diabetic patients should be monitored for:

1. Genital mycotic infections: More common adverse effect, particularly in women
2. Volume depletion: Monitor for signs of dehydration, especially in elderly patients or those on diuretics
3. Renal function: Regular monitoring of kidney function is recommended
4. Euglycemic diabetic ketoacidosis: Although rare, this can occur even in non-diabetic patients
5. Discontinuation before surgery: Stop at least 3 days before planned procedures 2

Special Considerations for Older Adults

For patients over 55 years:

• Volume status: Older adults are more susceptible to volume depletion; monitor closely
• Polypharmacy: Consider potential drug interactions with existing medications
• Renal function: More frequent monitoring of kidney function may be necessary
• Fall risk: Monitor for orthostatic hypotension, especially when initiating therapy 2

Contraindications

Empagliflozin should not be used in:

• Patients with severe hypersensitivity to the medication
• Pregnancy or breastfeeding
• Patients with severe genital mycotic infections
• Type 1 diabetes 2, 3

The cardiovascular and mortality benefits of empagliflozin in non-diabetic patients with established cardiovascular disease make it an important therapeutic option for this population, with a favorable risk-benefit profile when appropriate monitoring is implemented.